Nalepa I, Vetulani J
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Pol J Pharmacol. 1993 Mar-Apr;45(2):167-75.
The aim of this study was to compare the mechanisms of increased responsiveness of the beta-adrenoceptor dependent cyclic AMP generating system induced by chronic decrease of noradrenaline availability (beta-upregulation) with that resulting from simultaneous stimulation of alpha-adrenoceptors (alpha-potentiation) and to assess the role of protein kinase C in these phenomena. The beta-upregulation was produced by central chemosympathectomy with 6-hydroxydopamine. The role of alpha 1- and alpha 2-adrenoceptors was assessed by comparison of the effects of specific beta-adrenoceptor agonist isoproterenol with those of a mixed alpha-beta-adrenoceptor agonist noradrenaline, and clonidine was used to selectively stimulate alpha 2-adrenoceptors. The role of protein kinase C was assessed by measuring cyclic AMP responses in the presence and absence of 12-O-tetradecanoyl-phorbol 13-acetate. The results indicate that the mechanism of increased responsiveness induced by central chemosympathectomy is different from the alpha-potentiation, that only alpha 1-adrenoceptors are involved positively in alpha-potentiation, while the alpha 2-adrenoceptors play an inhibitory role, and that increased responsiveness following central chemosympathectomy may be inhibited by protein kinase C activation.
本研究的目的是比较因去甲肾上腺素可用性长期降低（β-上调）所诱导的β-肾上腺素能受体依赖性环磷酸腺苷生成系统反应性增加的机制，与同时刺激α-肾上腺素能受体（α-增强作用）所导致的该系统反应性增加的机制，并评估蛋白激酶C在这些现象中的作用。β-上调是通过用6-羟基多巴胺进行中枢化学交感神经切除术产生的。通过比较特异性β-肾上腺素能受体激动剂异丙肾上腺素与混合α-β-肾上腺素能受体激动剂去甲肾上腺素的作用，评估α1-和α2-肾上腺素能受体的作用，并用可乐定选择性刺激α2-肾上腺素能受体。通过在存在和不存在12-O-十四烷酰佛波醇13-乙酸酯的情况下测量环磷酸腺苷反应，评估蛋白激酶C的作用。结果表明，中枢化学交感神经切除术所诱导的反应性增加机制与α-增强作用不同，在α-增强作用中只有α1-肾上腺素能受体起正向作用，而α2-肾上腺素能受体起抑制作用，并且中枢化学交感神经切除术后反应性增加可能会被蛋白激酶C激活所抑制。
